The purposes of this project are to characterize changes in ability with aging in mice to develop and express delayed (tuberculin-type) hypersensitivity and to study reasons for these changes. Medium life span mice (A/Jax) are being used with the purified protein antigens conalbumin and methylated human serum albumin. In addition to measurement by repeated skin testings of delayed hypersensitivities to these two antigens that develop in groups of animals progressing in 3-month age steps through senility, collateral measurements are being made of this hypersensitivity in vitro, of peritoneal cell function, of anamnestic responses, of Arthus hypersensitivity, of primary and secondary humoral antibody production, and of age-related changes in A/Jax serum seen by two-dimensional electroimmunodiffusion analyses. A different experiment is examining premature aging of immunologic responses in SJL/J mice that makes the mice, starting about at 8 weeks of age, follow a trend opposite to that usually encountered in aging -- one of becoming more easily sensitized and less easily tolerized. We have found this effect seemingly associated with macrophage abnormalities. So the functions and characteristics of macrophages taken from SJL/J mice at different ages are being compared with those of macrophages taken from CF-1, CAF1, and A/Jax mice, and the reason for this macrophage change is being sought.